Novel Biomarkers for Cardiac Surgery-Associated Acute Kidney Injury: A Skeptical Assessment of Their Role

Cardiac surgery-associated acute kidney injury (AKI) is common and is associated with a high mortality rate. Traditional biomarkers of AKI (creatinine and urea) increase slowly in response to renal injury, are insensitive to mild degrees of AKI, and are influenced by nonrenal factors. There is considerable interest in novel biomarkers of AKI such as neutrophil gelatinase-associated lipocalin that increase rapidly after renal injury, detect mild degrees of AKI, and are less subject to nonrenal factors. It has been postulated that the early diagnosis of cardiac surgery-associated AKI using novel biomarkers will result in improved outcomes. However, there is little evidence that interventions started early in the course of evolving AKI enhance renal recovery. Until effective therapies are developed that significantly improve the outcome from AKI, there is little benefit from early diagnosis using novel biomarkers

Extracorporeal Membrane Oxygenation Clinical Dilemmas

Three scenarios are presented, based on real patients, illustrating various clinical dilemmas involving critical illness and extracorporeal membrane oxygenation (ECMO). The scenarios are outlined in the form of questions and answers. In most cases there is no single correct answer to the dilemmas presented. The pros and cons of particular interventions are discussed along with the actual treatment provided. In all cases, the ECMO circuit consisted of a polymethylpentene oxygenator (Quadrox PLS; MAQUET Cardiovascular, Hirlingen, Germany) and a centrifugal pump (Rotaflow; MAQUET Cardiovascular). Case 2 has been previously published as a letter to the editor (1)

Fooled by Significance Testing: An Analysis of the LOVIT Vitamin C Trial

In this article, I discuss the potential pitfalls of interpreting p values, confidence intervals, and declarations of statistical significance. To illustrate the issues, I discuss the LOVIT trial, which compared high-dose vitamin C with placebo in mechanically ventilated patients with sepsis. The primary outcome – the proportion of patients who died or had persisting organ dysfunction at day 28 – was significantly higher in patients who received vitamin C (p = .01). The authors had hypothesized that vitamin C would have a beneficial effect, although the prior evidence for benefit was weak. There was no prior evidence for a harmful effect of high-dose vitamin C. Consequently, the pretest probability for harm was low. The sample size was calculated assuming a 10% absolute risk difference, which was optimistic. Overestimating the effect size when calculating the sample size leads to low power. For these reasons, we should be skeptical that vitamin C causes harm in septic patients, despite the significant result. p-values and confidence intervals are probabilities concerning the chance of obtaining the observed data. However, we are more interested in the chance the intervention has a real effect on the outcome. That is to say, we are more interested in whether the hypothesis is true. A Bayesian approach allows us to estimate the false positive risk, which is the post-test probability there is no effect of the intervention. The false positive risk for the LOVIT trial (calculated from the published summary data using uniform priors for the parameter values) is 70%. Most likely, high-dose vitamin C does not cause harm in septic patients. Most likely it has no effect at all. If there is an effect, it is probably small and most likely beneficial

Troubleshooting Adult ECMO

The following scenarios explore some of the common problems encountered during extracorporeal membrane oxygenation (ECMO) in adults. In each scenario, the circuit is comprised of a centrifugal pump and a polymethylpentene oxygenator

Extracorporeal Membrane Oxygenation—Understanding the Evidence: CESAR and Beyond

Extracorporeal membrane oxygenation (ECMO) has been used for nearly 40 years for treating life threatening respiratory failure. Two historic randomized trials in adults, conducted using outdated techniques, did not show a survival advantage. However, recent case series and a large randomized controlled trial have demonstrated good outcomes from ECMO in adults. The CESAR trial, a large, multicenter, randomized trial comparing consideration for ECMO versus conventional therapy for treating severe acute respiratory failure in adults, has recently been published. The results and implications of this controversial trial are analyzed here, and a discussion of the problems inherent in assessing complex interventions in critically ill patients is provided. Additionally, the outcomes from ECMO from pandemic H1N1 influenza in Australia and New Zealand during the winter of 2009 are reviewed. Despite the inherent limitations of the methodology of the CESAR trial, the results support the use of ECMO in appropriately selected patients with life threatening acute respiratory failure. Treatments such as ECMO are extremely difficult to assess by randomized controlled trials. Observational data demonstrate excellent results from ECMO for treating patients with life threatening respiratory failure caused by pandemic H1N1 influenza, and have greatly influenced practice in Australia and New Zealand. Used as part of a multi-modal approach to treating acute respiratory failure in adults, ECMO is an important, potentially life saving, technique